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Physicochemical Profiling of Sartans: Detailed Study of Ionisation Constants and Distribution Coefficients

Tosco, Paolo
Rolando, Barbara
Fruttero, Roberta
Gasco, Alberto
Published in Helvetica Chimica Acta. 2008, vol. 91, p. 468-482
Abstract A detailed investigation of the ionization and lipophilicity profiles of selected sartans (valsartan, losartan, irbesartan, candesartan, candesartan cilexetil), a class of antihypertensives commonly used in therapy, is presented. The pKa macroconstants were determined by integrated potentiometry, capillary electrophoresis, and UV spectrophotometry. The measured pKa macroconstants were connected with the ionizable centers present in each molecule with the aid of model compounds. Potentiometric titrations with the GLpKa apparatus were performed to determine the distribution profile (logD vs. pH) of valsartan, while the shake-flask procedure was used to characterize the distribution profile of the other compounds. Valsartan showed a lipophilicity profile consistent with the presence of two acidic centers. Losartan and irbesartan, which contain one acidic and one basic center, displayed the classical bellshaped profile of ordinary ampholytes. By contrast, a more complex situation emerged in the case of candesartan, due to the large number of ionization equilibria involved. The low solubility of candesartan cilexetil, together with the ease of hydrolysis of the ester moiety, prevented a successful investigation of its ionization and lipophilicity profiles.
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TOSCO, Paolo et al. Physicochemical Profiling of Sartans: Detailed Study of Ionisation Constants and Distribution Coefficients. In: Helvetica Chimica Acta, 2008, vol. 91, p. 468-482. doi: 10.1002/hlca.200890051 https://archive-ouverte.unige.ch/unige:4004

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Deposited on : 2009-11-10

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